The objectives of this proposal are: 1) To characterize the background, behavior and physiological characteristics of children vulnerable to depressive illness, namely the offspring of parents with diagnoses of unipolar, bipolar illness; 2) To determine the degree of stress in the family environment and its relation to the presence of symptoms in vulnerable children; 3) To study the effect of mild stress upon physiological responsivity in these children; 4) to study the behavior and physiological characteristics of children hospitalized because of severe depressive symptoms; and 5) to determine the therapeutic efficacy and physiological effects of antidepressant drug treatment of severely depressed children. In the first study approximately 20 to 30 children in each of three groups (normals, unipolar and bipolar offspring) will be interviewed and tested with a physiologic battery to measure reactivity to mild stress (cold pressor and loud sound) and to determine autonomic balance. A structured interview with the child and parents will provide behavioral information which will be supplemented by teacher and parent ratings. Blind raters will score interviews from video tapes in order to accurately characterize the sample. The hospital study will involve 30 children who meet screening criteria for severe depression. They will be treated with imipramine or placebo in a random assignment, double blind study with pre- and post-treatment baseline phases. As with the other subjects, all-night EEG sleep and autonomic measures will be obtained to test predictions from a theory linking depression to a biphasic autonomic shift resulting from genetic-stress interaction.